The Robert Brigham Multidisciplinary Clinical Research Center is the principal resource for clinical, translational, epidemiologic, health services and methodological research on rheumatologic and musculoskeletal conditions at Brigham and Women's Hospital, and throughout the Harvard Medical and Public Health communities. The objectives of the Center are to: 1) perform cutting edge research on rheumatological and musculoskeletal problems to prevent these disorders;improve their management;enhance quality of life for patients with these problems;and optimize provision of services for these conditions;and 2) provide core resources and intellectual leadership to catalyze such research throughout the Center's extensive research base. We propose three innovative, high impact projects that span a wide range of clinical problems and methodological approaches, reflecting the breadth of the Center. The first is a population-based study of the rates and predictors of failure of total hip replacement (THR), leading to a revision, among Medicare beneficiaries. The project is highly significant given the enormous cost and disability associated with failure of THR, the scarcity of data on predictors of failure, and the absence of population based data on THR failure in the US. The second project is a translational research study of endothelial dysfunction in patients with rheumatoid arthritis. We will determine whether endothelial dysfunction is 1) more common in patients with RA than in age-matched controls, 2) predictive of cardiac sequelae, and 3) responsive to therapy with biologies. The project has the potential to create a new treatment paradigm for managing CVD in patients with OA. The third project is a randomized controlled trial of a theory-based, multi-modal intervention to reduce the incidence of lower extremity injuries in 14-18 year old female basketball players. This study is particularly significant because of the rapid increase in sports injuries among females, and the well documented association between lower extremity injury and subsequent osteoarthritis. We propose a Methodology core whose personnel work closely with each MCRC project to ensure the most rigorous methods and also with investigators in the research base, on a cost share basis. Finally, we propose an Administrative Core that will facilitate strategic and operational decision making and activities in the Center. The Brigham and Womens Hospital MCRC has been continuously funded since 1977. Initially under the direction of Matthew Liang, MD, the Center has trained many of the preeminent leaders in rheumatology today, including the current Director, Jeffrey Katz, MD, who was mentored by Dr. Liang for many years. The Center's strengths include a solid tradition of highly successful research, and close collaboration with colleagues in many disciplines, especially orthopaedic surgery. The current annual budget exceeds $3 million, with over 70 active protocols, and 28 investigators and staff. All the proposed projects are clinical.